The general objective of the research proposal will be to determine the role of nutrition in the metabolism of aflatoxin B1 (AFB1) and certain substrates of 'drub metabolizing' enzymes as a means of evaluating the role of nutrition in the toxicities of carcinogens and other foreign compounds. Specific objectives are designed to elucidate the effects of protein and vitamin A deficiencies on the activities of these enzymes, which are primarily the hepatic mixed function oxidase, the epoxide hydrase, and the various transferases. The concerted activities of these enzymes on the quantities of reactive AFB1 metabolite(s) produced and the subsequent binding of the metabolite(s) to critical macromolecules will be evaluated during the deficiency state. The toxicological significance of these biochemical effects will be evaluated. These biochemical events will be quantitatively manipulated both by dietary modification of the nutrient under study as well as by the administration of various inducers and inhibitors of critical enzyme activities. In this way alteration of selected rates of metabolism and/or other biochemical events will be compared with the toxicity produced. Toxicity will be evaluated both in short-term tests by examination of the degree of hepatic necrosis produced and in long term tests by determination of tumor yield. An understanding of the specific mechanism(s) of such interactions should be informative both with regard to 1) the role of the nutrient and 2) the essentiality of the proposed 'ultimate' carcinogenic intermediate in the lesion. A fundamental understanding of the type of interaction could be extended to the role of metabolism in the toxicities of other foreign compounds.